Official Project Description
These simulations are exploring the landscape of the dimer pantothenate kinase 1 from humans.
This enzyme is the rate-limiting step in the synthesis of Acetyl-CoA, and is widely expressed across many tissues.
The enzyme processes vitamin B5 (pantothenate) yielding phosphopantothenate, which is then worked up by other enzymes into Acetyl-CoA.
Acetyl-CoA binds to the same site as pantothenate, and thus prevents the enzyme from overproducing pantothenate through product inhibition.
These simulations are part of an effort to identify conformations that are important for other inhibitors of that site.
Being able to control when the enzyme is productive regardless of whether AcCoA is abundant gives a framework for manipulating cellular metabolism and signalling in many diseases, particularly diabetes. This simulation, because it is ligand free, will advance the state of research on this important protein, so that subsequent studies can better understand modulating compounds relevant to particular diseases.